A Novel One-Transistor Dynamic Random-Access Memory (1T DRAM) Featuring Partially Inserted Wide-Bandgap Double Barriers for High-Temperature Applications.

These days, the demand on electronic systems operating at high temperature is increasing owing to bursting interest in applications adaptable to harsh environments on earth, as well as in the unpaved spaces in the universe. However, research on memory technologies suitable to high-temperature conditions have been seldom reported yet. In this work, a novel one-transistor dynamic random-access memory (1T DRAM) featuring the device channel with partially inserted wide-bandgap semiconductor material toward the high-temperature application is proposed and designed, and its device performances are investigated with an emphasis at 500 K. The possibilities of the program operation by impact ionization and the erase operation via drift conduction by a properly high drain voltage have been verified through a series of technology computer-aided design (TCAD) device simulations at 500 K. Analyses of the energy-band structures in the hold state reveals that the electrons stored in the channel can be effectively confined and retained by the surrounding thin wide-bandgap semiconductor barriers. Additionally, for more realistic and practical claims, transient characteristics of the proposed volatile memory device have been closely investigated quantifying the programming window and retention time. Although there is an inevitable degradation in state-1/state-0 current ratio compared with the case of room-temperature operation, the high-temperature operation capabilities of the proposed memory device at 500 K have been confirmed to fall into the regime permissible for practical use.

Effects of the duty ratio on the niobium oxide film deposited by pulsed-DC magnetron sputtering methods.

Niobium oxide (Nb2O5) films were deposited on p-type Si wafers and sodalime glasses at a room temperature using in-line pulsed-DC magnetron sputtering system with various duty ratios. The different duty ratio was obtained by varying the reverse voltage time of pulsed DC power from 0.5 to 2.0 micros at the fixed frequency of 200 kHz. From the structural and optical characteristics of the sputtered NbOx films, it was possible to obtain more uniform and coherent NbOx films in case of the higher reverse voltage time as a result of the cleaning effect on the Nb2O5 target surface. The electrical characteristics from the metal-insulator-semiconductor (MIS) fabricated with the NbOx films shows the leakage currents are influenced by the reverse voltage time and the Schottky barrier diode characteristics.

Emergence and spread of carbapenem-resistant Acinetobacter baumannii sequence type 191 in a Korean hospital.

Emergence and spread of specific carbapenem-resistant Acinetobacter baumannii (CRAB) clones cause a serious therapeutic problem. This study was aimed to investigate the clonal diversity and genetic basis of antimicrobial resistance among the 69 CRAB isolates from 2009 to 2010 in a Korean hospital. All CRAB isolates were found to be sequence type (ST) 2 using the Institute Pasteur's multilocus sequence typing (MLST) scheme, but classified into two sequence groups and nine pulsotypes. Fifty-six CRAB isolates belonging to two main pulsotypes were found to be ST191 using the Bartual's MLST scheme. All CRAB isolates showed an extensively drug-resistant phenotype. The blaOXA-51/blaOXA-23, blaAmpC/blaPER-1 and armA genes were largely responsible for resistance to carbapenems, extended-spectrum ß-lactams and aminoglycosides, respectively. The first CRAB strains identified in 2005 in this hospital were found to be ST2 using the Institute Pasteur's MLST scheme, but showed ST353 using the Bartual's MLST scheme and different pulsotypes from the CRAB isolates from 2009 to 2010. In conclusion, this is the first report of emergence and spread of A. baumannii ST191 in Korea, as well of the genetic basis of its antimicrobial resistance.

Bio-inspired catechol chemistry: a new way to develop a re-moldable and injectable coacervate hydrogel.

A new way is demonstrated to develop a bio-inspired coacervate hydrogel by following catechol chemistry showing injectable and re-moldable physical properties. The formed coacervate shows potential long-term stability under water. Depending on pH, formation of the coacervate has been verified which is confirmed by XPS and zeta potential measurements.

New phytopharmaceutical agent CJ-20001 modulates stress-induced inflammatory infiltration into gastric mucosa.

BACKGROUND/AIMS: CJ-20001 is a phytopharmaceutical agent and currently being investigated in a Phase II trial for the treatment of acute and chronic gastritis patients in Korea. In this study we addressed the protective effects of CJ-20001 against water immersion restraint stress (WIRS)-induced gastric injury in rats and studied the underlying mechanisms. METHODOLOGY: To evaluate the protective effect of CJ-20001 on stress-induced gastric lesions, rats were exposed to water immersion restraint stress. Inflammatory infiltration into gastric mucosa was examined by immunohistochemistry and in vitro invasion assay. Expression of proinflammatory cytokines was detected with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Pretreatment with CJ-20001 dose-dependently attenuated the WIRS-induced gastric lesions as demonstrated by gross pathology and histology. WIRS increased infiltration of mast cells and macrophages into the gastric mucosa and submucosal layer, whereas the inflammatory infiltration was markedly inhibited by CJ-20001 administration. An in vitro cell invasion assay showed that treatment with CJ-20001 decreased the migration of macrophages. CJ-20001 suppressed the expression of proinflammatory cytokines, IL-18, IP-10 and GRO/KC, in lipopolysaccharides (LPS)-treated macrophages. CONCLUSIONS: These data suggest that novel phytopharmaceutical agent CJ-20001 has the potent anti-inflammatory properties through inhibition of inflammatory infiltration in psycho-physiological stress-induced gastric injury.

Characterization of sodium hyaluronate blends using frit inlet asymmetrical flow field-flow fractionation and multiangle light scattering.

We characterized ultrahigh molecular weight sodium hyaluronate (NaHA) and blended pharmaceutical products containing NaHA using flow field-flow fractionation and multiangle light scattering-differential refractive index (FlFFF-MALS-DRI). NaHA is a water-soluble polysaccharide with a range of molecular weights (MW; 10(5)~10(8) Da) that is found in body fluids and tissues. NaHA is also used commercially in pharmaceutical and cosmetic applications. We used a frit inlet asymmetrical FlFFF channel to separate aqueous polymers according to their hydrodynamic size, and we used on-line measurements of light scattering to obtain the MW distribution (MWD) as well as structural information about NaHA in aqueous solution. In this study, we investigated NaHA and anti-adhesive blend mixtures of NaHA (a commercial NaHA blend mixture containing sodium carboxymethyl cellulose and a new blend with hydroxyethyl starch (HES)) to determine the molecular weight distribution MWD of NaHA and the blend mixtures and to obtain structural information about these compounds in aqueous solution. We also examined the characteristics of NaHA-HES-polylactic-co-glycolic acid film products exposed to gamma radiation for sterilization purposes.

Improved synthesis of hyaluronic acid hydrogel and its effect on tissue augmentation.

HA-HMDA hydrogels were developed by direct amide bond formation between the carboxyl groups of hyaluronic acid (HA) and hexamethylenediamine (HMDA) with an optimized carboxyl group modification in the preliminary experiment. However, these HA-HMDA hydrogels transformed into an unstable liquid form after steam sterilization, and were problematic for application to actual dermal filler. A new method to overcome the problem of the previously developed HA-HMDA hydrogels is to prepare them by adjusting the pH in this study. Not only are these improved HA-HMDA hydrogels prepared with lower amounts of cross-linking and activation agents compared to the previously developed hydrogels, but they also maintain a stable form after steam sterilization. These improved HA-HMDA hydrogels showed higher viscoelasticity and longer lasting effects than the previous ones, despite the fact that the amount of the HMDA used as a cross-linking agent as well as 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrated (HOBt) used as activation agents were substantially reduced. According to an in vivo test using a wrinkled mouse model, the improved HA-HMDA hydrogels exhibited significantly improved tissue augmentation effects compared to a positive control of Restylane, which is widely used for the tissue augmentation throughout the world. Furthermore, histological analysis revealed excellent biocompatibility and safety of the improved synthesized HA-HMDA hydrogels.

SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor.

The extracts of earth worms, Eisenia andrei, have been used as a therapeutic agent for stroke in the traditional medicine. It is also reported that the protease fraction separated from the extracts has strong anti-thrombotic activity. Besides anti-thrombotic actions, we found that SP-8203, N-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl]-N-{4-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino]butyl}acetamide, derived from the extracts of earth worms blocked N-methyl-(D)-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. The neuroprotective effects of SP-8203 were attributable to prevention of Ca(2+) influx through NMDA receptors. The systemic administration of SP-8203 markedly reduced neuronal death following middle cerebral artery occlusion in rats. SP-8203 significantly improved spatial learning and memory in the water maze test. These results provided strong pharmacological basis for its potential therapeutic roles in cerebral ischemia.

SP-8203 reduces oxidative stress via SOD activity and behavioral deficit in cerebral ischemia.

Both oxidative stress and excessive activation of glutamate receptors are implicated as major causes of ischemic brain injury. However, the existing N-methyl-D-aspartate (NMDA) receptor antagonists have not exerted good clinical outcome, most likely because they do not protect neurons against oxidative stress. Thus, more effective glutamate antagonists and antioxidants are needed for the treatment of ischemic stroke. In previous study, SP-8203, derived from earth worms, showed the blocking effect of NMDA receptor. We provided evidence that SP-8203 could also suppress the oxidative stress in this study. In vitro, 250 µM H2O2 was treated to SH-SY5Y cells after the pre-treatment of SP-8203 (2, 20 and 200 µM). SP-8203 significantly suppressed H2O2-induced cell death and reactive oxygen species production. In addition, we investigated the effects of SP-8203 in middle cerebral artery (MCA) occluded rat model. SP-8203 (5 and 10 mg/kg) was administered intraperitoneally to rats before and after the MCA occlusion and was injected daily for 10 days. After 10 days, SP-8203 remarkably reduced brain infarct volume and lipid peroxidation products in the MCA-occluded rats but MK-801 didn't. Moreover, SP-8203 significantly improved neurological deficits such as shortening of latency time in Rota rod performance. However, MK-801 didn't improve behavioral deficits. Therefore, SP-8203 may be more effective for multiple-target mechanisms of ischemic stroke.

Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei.

To investigate the intestinal absorption of a fibrinolytic and proteolytic lumbrokinase extracted from Eisenia andrei, we used rat everted gut sacs and an in situ closed-loop recirculation method. We extracted lumbrokinase from Eisenia andrei, and then raised polyclonal antibody against lumbrokinase. Fibrinolytic activity and proteolytic activity in the serosal side of rat everted gut sacs incubated with lumbrokinase showed dose- and time-dependent patterns. Immunological results obtained by western blotting serosal side solution using rat everted gut sacs method showed that lumbrokinase proteins between 33.6 and 54.7 kDa are absorbed mostly by the intestinal epithelium. Furthermore, MALDI-TOF mass spectrometric analysis of plasma fractions obtained by in situ recirculation method confirmed that lumbrokinase F1 is absorbed into blood. These results support the notion that lumbrokinase can be absorbed from mucosal lumen into blood by oral administration.

Effect of cross-linking reagents for hyaluronic acid hydrogel dermal fillers on tissue augmentation and regeneration.

A novel, biocompatible, and nontoxic dermal filler using hyaluronic acid (HA) hydrogels was successfully developed for tissue augmentation applications. Instead of using highly reactive cross-linkers such as divinyl sulfone (DVS) for Hylaform, 1,4-butanediol diglycidyl ether (BDDE) for Restylane, and 1,2,7,8-diepoxyoctane (DEO) for Puragen, HA hydrogels were prepared by direct amide bond formation between the carboxyl groups of HA and hexamethylenediamine (HMDA) with an optimized carboxyl group modification for effective tissue augmentation. The HA-HMDA hydrogels could be prepared within 5 min by the addition of HMDA to HA solution activated with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrate (HOBt). Five kinds of samples, a normal control, a negative control, a positive control of Restylane, adipic acid dihydrazide grafted HA (HA-ADH) hydrogels, and HA-HMDA hydrogels, were subcutaneously injected to wrinkled model mice. According to the image analysis on dorsal skin augmentation, the HA-HMDA hydrogels exhibited the best tissue augmentation effect being stable longer than 3 months. Furthermore, histological analyses after hematoxylin-eosin (H&E) and Masson's trichrome staining revealed the excellent biocompatibility and safety of HA-HMDA hydrogels. The dermal thickness and the dermal collagen density in wrinkled mice after treatment with HA-HMDA hydrogels for 12 weeks were comparable to those of normal mice. Compared with HA-DVS hydrogels and Restylane, the excellent tissue augmentation by HA-HMDA hydrogels might be ascribed to the biocompatible residues of amine groups in the cross-linker of HMDA. The HA-HMDA hydrogels will be investigated further as a novel dermal filler for clinical applications.

Depolymerization study of sodium hyaluronate by flow field-flow fractionation/multiangle light scattering.

Thermal depolymerization of ultrahigh-molecular-weight (UHMW) sodium hyaluronate (NaHA) was studied systematically by using frit-inlet asymmetrical flow field-flow fractionation/multiangle light scattering/differential refractive index (FI-AFlFFF/MALS/DRI). FI-AFlFFF was utilized for the size separation of NaHA samples which had been thermally degraded for varied treatment times, followed by light-scattering detection to determine MW and structural information of degraded NaHA products. Analysis of NaHA products showed time-dependent depolymerization of raw molecules into smaller-MW components, as well as unfolding of compact structures of UHMW NaHA. To determine whether the observed decrease in MW of sodium hyaluronate originated from the chain degradation of UHMW molecules or from dissociation of entangled complex particles that may have been formed by intermolecular association, narrow size fractions (1 x 10(7)-6 x 10(7) and >6 x 10(7) MW) of NaHA molecules were collected during FlFFF separation and followed by thermal treatment. Subsequent FI-AFlFFF/MALS analysis of collected fractions after thermal treatment suggested that the ultrahigh-MW region (>10(7) Da) of NaHA is likely to result from supermolecular structures formed by aggregation of large molecules.

Flow field-flow fractionation/multiangle light scattering of sodium hyaluronate from various degradation processes.

Sodium hyaluronate (NaHA) is an ultrahigh molecular weight polysaccharide that is found in body tissues, synovial fluid, the vitreous humor, and the umbilical cord, and the size characterization of NaHA is important in pharmaceutical applications. On-line field-flow fractionation/multiangle light scattering/differential refractive index (FlFFF/MALS/DRI) has been applied for the study of degradation efficiency of sodium hyaluronate (NaHA). A NaHA raw sample was degraded by different chemical or physical methods and the degraded NaHA samples were separated using field-programming FlFFF, in which separation is achieved by differences in diffusion coefficients or hydrodynamic diameters. Separation was followed by serial detection using MALS and DRI. Molecular weight distribution (MWD) and information relating to the radius of gyration of the NaHA samples were examined for the raw and degraded NaHA samples. Samples studied include: two different products of ultrasonic degradation, two products of alkaline degradation, and four different products of enzymatic degradation. While alkaline degradation showed a moderate degradation compared to ultrasonic and enzymatic methods in reducing average MW, the latter two degradation methods showed significant changes in average molecular weight and in conformation of NaHA.

Control of the molecular degradation of hyaluronic acid hydrogels for tissue augmentation.

A novel protocol to control the molecular degradation of hyaluronic acid (HA) hydrogels was successfully developed for tissue augmentation applications. HA has a different conformational structure in water and organic solvent, and the carboxyl group of HA is known to be the recognition site of hyaluronidase and HA receptors. Based on these findings, HA was chemically modified by grafting adipic acid dihydrazide (ADH) to the carboxyl group of HA in the water to prepare HA-ADH(WATER) and in the mixed solvent of water and ethanol to prepare degradation-controlled HA-ADH(WATER/ETHANOL). Three kinds of HA hydrogels were prepared by the crosslinking of HA-ADH(WATER) or HA-ADH(WATER/ETHANOL) with bis(sulfosuccinimidyl) suberate, and by the crosslinking of HA-OH with divinyl sulfone (DVS). In vitro and in vivo degradation tests showed that HA-DVS hydrogels were degraded most rapidly, followed by HA-ADH(WATER) hydrogels and HA-ADH(WATER/ETHANOL) hydrogels. There was no adverse effect during and after in vivo degradation tests. All of the HA hydrogel samples appeared to be biocompatible, according to the histological analysis with hematoxylin-eosin and Alcian blue.

Molecular weight and structure characterization of sodium hyaluronate and its gamma radiation degradation products by flow field-flow fractionation and on-line multiangle light scattering.

A combined flow field-flow fractionation (FlFFF)/multiangle light scattering (MALS)/differential refractive index (DRI) detection method has been utilized for the size fractionation and characterization of ultrahigh molecular weight (MW) sodium hyaluronate (NaHA) samples. Separation of broad MW NaHA polymers was carried out by a frit inlet asymmetrical FlFFF channel employed with a linear field programming method followed by the on-line monitoring of light scattering at multiple angles for the calculation of MW and for the study of the conformation of NaHA samples. NaHA samples examined were: (1) two different viscosity fractions of NaHA obtained by a refinement process and (2) NaHA products of gamma radiation degradation. While the NaHA samples of two different viscosity fractions exhibited clearly different MW distributions and similar conformation, the radiation degraded NaHA samples showed a clear difference in both MW distribution and polymer structure.

Antithrombotic effects by oral administration of novel proteinase fraction from earthworm Eisenia andrei on venous thrombosis model in rats.

A novel proteinase fraction, SPP-501, was purified from the earthworm, Eisenia andrei, and its antithrombotic effects compared with those of urokinase and t-PA (tissue type-plasminogen activator) in a thrombosis model, induced by the insertion of a stainless wire coil into the inferior vena cava. SPP-501, urokinase and t-PA were administrated once a day for 14 days. On the oral administration of SPP-501, as well as urokinase and t-PA, the thrombus weight was dramatically decreased. The euglobulin lysis time (ELT) was also shortened by SPP-501, but urokinase and t-PA failed to dissolve the euglobulin clot. Conversely, urokinase and t-PA produced detectable fibrinogen/fibrin degradation products (FDP), but SPP-501 did not. Thrombin induced platelet aggregation was desensitized in the SPP-501 treatment groups. With a high dose of SPP-501 (45 mg/kg), the APTT (activated partial thromboplastin time) was prolonged. These results suggest that SPP-501 shows both antithrombotic and fibrinolytic activities when orally administered.

Effect of dissolution temperature on the structures of sodium hyaluronate by flow field-flow fractionation/multiangle light scattering.

Molecular weight distribution (MWD) and structural deformation of ultrahigh molecular weight (MW) sodium hylaluronate (10(5)-10(8) g/mol) were studied under different sample dissolution temperature conditions, using on-line flow field-flow fractionation (FlFFF) and multiangle light scattering (MALS). Sodium hyaluronate (NaHA) materials from sarcoma fluid have been studied by dissolving them in water at three different temperature conditions (5 degrees C, 50 degrees C, and 90 degrees C). Frit inlet asymmetrical flow field-flow fractionation (FI-AFlFFF), with field programming, was utilized for the separation of NaHA by MW, and on-line observation of light scattering of fractionated NaHA by MALS was performed in order to determine the MWD and molecular conformation. In these experiments, NaHA molecules exhibited an extended structure from a formerly rather compact geometry when the dissolving temperature was raised to 90 degrees C. This study also showed a clear difference in the MWD of NaHA when a preliminary filtration process was applied.

Molecular cloning, sequencing, and expression of a fibrinolytic serine-protease gene from the earthworm Lumbricus rubellus.

The full-length cDNA of the lumbrokinase fraction 6 (F6) protease gene of Lumbricus rubellus was amplified using an mRNA template, sequenced and expressed in E. coli cells. The F6 protease gene consisted of pro- and mature sequences by gene sequence analysis, and the protease was translated and modified into active mature polypeptide by N-terminal amino acid sequence analysis of the F6 protease. The pro-region of F6 protease consisted of the 44 residues from methionine-1 to lysine-44, and the mature polypeptide sequence (239 amino acid residues and one stop codon; 720 bp) started from isoleucine-45 and continued to the terminal residue. F6 protease gene clones having pro-mature sequence and mature sequence produced inclusion bodies in E. coli cells. When inclusion bodies were orally administrated rats, generated thrombus weight in the rat's venous was reduced by approximately 60 % versus controls. When the inclusion bodies were solubilized in pepsin and/or trypsin solutions, the solubilized enzymes showed hemolytic activity in vitro. It was concluded the F6 protease has hemolytic activity, and that it is composed of pro- and mature regions.

Purification and characterization of six fibrinolytic serine-proteases from earthworm Lumbricus rubellus.

The six lumbrokinase fractions (F1 to F6) with fibrinolytic activities were purified from earthworm Lumbricus rubellus lysates using the procedures of autolysis, ammonium sulfate fractionation, and column chromatography. The proteolytic activities on the casein substrate of the six iso-enzymes ranged from 11.3 to 167.5 unit/mg with the rank activity orders of F2 > F1 > F5 > F6 > F3 > F4. The fibrinolytic activities of the six fractions on the fibrin plates ranged from 20.8 to 207.2 unit/mg with rank orders of F6 > F2 > F5 > F3 > F1 > F4. The molecular weights of each iso-enzyme, as estimated by SDS-PAGE, were 24.6 (F1), 26.8 (F2), 28.2 (F3), 25.4 (F4), 33.1 (F5), and 33.0 kDa (F6), respectively. The plasminogen was activated into plasmin by the enzymes. The optimal temperature of the six iso-enzymes was 50 degrees C, and the optimal pH ranged from pH 4-12. The four iso-enzymes (F1-F4) were completely inhibited by PMSF. The two enzymes (F5 and F6) were completely inhibited by aprotinin, TLCK, TPCK, SBTI, LBTI, and leupeptin. The N-terminal amino acid (aa) sequences of the first 20 to 22 residues of each fraction had high homology. All six iso-enzymes had identical aa residues 2-3 and 13-15. The N-terminal 21-22 aa sequences of the F2, F3, and F4 iso-enzymes were almost the same. The N-terminal aa sequences of F5 and F6 were identical.